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JCEM Case Reports Sep 2023Primary pituitary T-lymphoblastic lymphoma is a rare clinical entity. A 45-year-old woman presented with headache, left-eye blurry vision, diplopia, ophthalmoplegia, and...
Primary pituitary T-lymphoblastic lymphoma is a rare clinical entity. A 45-year-old woman presented with headache, left-eye blurry vision, diplopia, ophthalmoplegia, and ptosis. Magnetic resonance imaging of the brain showed a sellar mass most likely consistent with a pituitary macroadenoma. Laboratory evaluation disclosed secondary hypothyroidism, secondary adrenal insufficiency, and hyperprolactinemia. The mass was removed by transsphenoidal resection, and subsequent immunophenotyping revealed T-cell lymphoblastic lymphoma. Secondary workup confirmed lymphomatous confinement to the central nervous system. Following resection, the patient's headaches improved, but she experienced persistent visual deficits and palsies of cranial nerves III, IV, and VI. The chemotherapy regimen consisted of high-dose methotrexate, followed by alternating cycles of cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (Adriamycin), dexamethasone (cyclophosphamide, mesna, vincristine sulfate, doxorubicin hydrochloride, dexamethasone), and methotrexate/cytarabine. Since receiving chemotherapy, there has been an improvement in numbness, ptosis, left orbital pressure, and headaches. This case represents only the eighth example of T-cell primary pituitary lymphoma, and the youngest patient to receive the diagnosis.
PubMed: 37908217
DOI: 10.1210/jcemcr/luad097 -
Clinical Lymphoma, Myeloma & Leukemia Sep 2019Multiple myeloma (MM) usually follows a clinical course leading to refractoriness and limited treatment options in advanced stages, which might need bridge therapies to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple myeloma (MM) usually follows a clinical course leading to refractoriness and limited treatment options in advanced stages, which might need bridge therapies to either autologous stem cell transplantation or novel therapies. We report our experience with the high-dose chemotherapy mCBAD (modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone) regimen in newly diagnosed MM (NDMM), relapsed/refractory MM (RRMM), and plasma cell leukemia (PCL) patients.
PATIENTS AND METHODS
We searched our electronic records database for MM patients who received mCBAD from 2010 to 2016 for 28-day cycles of cyclophosphamide 350 mg/m intravenously (I.V.) twice daily with mesna 400 mg/m I.V. daily (days 1-4), bortezomib 1.3 mg/m subcutaneously/I.V. (days 1, 4, 8, 11), doxorubicin 9 mg/m daily continuous infusion (days 1-4), dexamethasone 40 mg orally daily (on days 1-4, 9-12, 17-20). International Myeloma Working Group (IMWG) criteria were used for response assessment and diagnosis. Descriptive statistics, Fisher exact test, χ, Wilcoxon rank sum, and Kaplan-Meier were used for statistical purposes.
RESULTS
One hundred forty patients met the inclusion criteria. A median of 2 cycles of therapy was administered. The overall response rate was 85% in patients with RRMM (n = 116) and 100% in NDMM (n = 13) and PCL (n = 11) patients. Respective median progression-free survival (mPFS) for NDMM, PCL, and RRMM were 19.61 months (95% confidence interval [CI], 5.26 to not applicable [NA]), 7.56 months (95% CI, 4.7 to NA), and 4.64 months (95% CI, 3.75-6.73). Patients with RRMM who used mCBAD as a bridge to autologous transplant (36.2%) had mPFS (11.48 months; 95% CI, 7.52-15.9 months) compared with those who did not (mPFS: 3.19 months; 95% CI, 2.4-3.75 months). Cytopenias occurred in more than 90% of patients, and febrile neutropenia was noted in 26%. All cases of treatment-related mortality (8%) occurred in patients with RRMM, except for 1 patient with PCL.
CONCLUSION
mCBAD results in high response rates in myeloma and PCL, however, with high treatment-related mortality. Its use in RRMM should be limited to patients who have immediate need for therapy without other treatment options and who have good performance status (score of 0-1) or NDMM if novel agents are not available depending on practice setting. mCBAD can be a treatment option for patients with PCL.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Resistance, Neoplasm; Female; Humans; Leukemia, Plasma Cell; Male; Middle Aged; Multiple Myeloma; Neoplasm Staging; Prognosis; Recurrence; Research Design; Retreatment; Treatment Outcome; Young Adult
PubMed: 31201134
DOI: 10.1016/j.clml.2019.05.001 -
The Journal of Biological Chemistry May 20222-Ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC) is a member of the flavin and cysteine disulfide containing oxidoreductase family (DSOR) that catalyzes the...
2-Ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC) is a member of the flavin and cysteine disulfide containing oxidoreductase family (DSOR) that catalyzes the unique reaction between atmospheric CO and a ketone/enolate nucleophile to generate acetoacetate. However, the mechanism of this reaction is not well understood. Here, we present evidence that 2-KPCC, in contrast to the well-characterized DSOR enzyme glutathione reductase, undergoes conformational changes during catalysis. Using a suite of biophysical techniques including limited proteolysis, differential scanning fluorimetry, and native mass spectrometry in the presence of substrates and inhibitors, we observed conformational differences between different ligand-bound 2-KPCC species within the catalytic cycle. Analysis of site-specific amino acid variants indicated that 2-KPCC-defining residues, Phe501-His506, within the active site are important for transducing these ligand induced conformational changes. We propose that these conformational changes promote substrate discrimination between H and CO to favor the metabolically preferred carboxylation product, acetoacetate.
Topics: Acetoacetates; Carbon Dioxide; Carboxy-Lyases; Catalysis; Ligands; Mesna; Oxidoreductases; Xanthobacter
PubMed: 35367206
DOI: 10.1016/j.jbc.2022.101884 -
Journal of Oncology Pharmacy Practice :... Jan 2024The lack of anticancer drugs for curative and supportive purposes is the critical reason for the low survival rate in low-and-middle-income countries. This study aims to... (Observational Study)
Observational Study
OBJECTIVE
The lack of anticancer drugs for curative and supportive purposes is the critical reason for the low survival rate in low-and-middle-income countries. This study aims to analyze whether the National Essential Medicines List (NEML) and Registered Essential Medicines List (REML) are in concordance with the World Health Organization (WHO) Essential Medicines List (EML) and whether the formularies prevalent in the country are parallel to each other and to the NEML.
METHOD
An observational study design was used in which antineoplastic drugs from the 2021 NEML and REML were compared with 2021 WHO EML to evaluate their availability in Pakistan. Market access was determined. Moreover, the formularies of six different hospital types were compared with each other and with the NEML, and REML to estimate the availability within hospitals.
RESULTS
There were 66 anticancer drugs in 2021 WHO EML and all were found in Pakistan's 2021 NEML but only 48 drugs (73%) were found in the REML. Hydroxycarbamide and dasatinib were two registered drugs absent in all hospitals' formularies. The market access for anticancer medicines was 73% (48 of 66). Semigovernment hospital (86%) has the highest availability, followed by the government hospital (80%). All the hospitals have unregistered drugs including bortezomib, lenalidomide, and mesna.
CONCLUSION
Pakistan's NEML adopts WHO EML abruptly but all medicines are not registered. The hospitals are trying their best to increase availability but optimum drug regulations to revise NEML based on the country's requirements and emphasizing registration of anticancer medicines are needed to improve the country's availability of antineoplastic agents.
Topics: Humans; Pakistan; Antineoplastic Agents; World Health Organization; Drugs, Essential; Bortezomib
PubMed: 37006130
DOI: 10.1177/10781552231167809 -
World Journal of Clinical Cases Jul 2023Angiosarcoma (AS) is a rare and highly aggressive soft tissue disease that most commonly arises in deep soft tissues. There are only a few reported cases of AS involving...
BACKGROUND
Angiosarcoma (AS) is a rare and highly aggressive soft tissue disease that most commonly arises in deep soft tissues. There are only a few reported cases of AS involving the ovary and even fewer reports of the underlying molecular abnormalities. Here, we briefly review two cases of primary ovarian AS (oAS) with specific molecular events and immune checkpoints. The clinical features and prognosis of the disease, diagnosis, differential diagnosis, and new treatment approaches are discussed based on a literature review.
CASE SUMMARY
Case 1: A 51-year-old female patient was admitted with right lower limb pain for 5 mo, and lower abdominal pain with hematuria for 1 mo. Partial removal of rectus abdominis muscle and fascia, partial hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy were performed. Pathology revealed primary oAS. Fluorescence hybridization revealed gene amplification. MESNA + ADM + IFO + DTIC (MAID) regimen was administered, but stable disease was achieved. The patient died 1 mo later. Case 2: A 41-year-old female patient presented with fatigue, nausea, decreased appetite, and diffuse abdominal pain. On physical examination, the abdomen was distended and a complex cystic mass was palpable in the right pelvic cavity. Pathology revealed primary oAS. MAID chemotherapy was administered and programmed death ligand 1 (PD-L1) staining was performed on the tumor samples. The patient benefited from anti-PD-1 immunotherapy and is alive without any evidence of disease 27 mo off therapy in follow-up.
CONCLUSION
Long-term survival benefit for primary oAS can be achieved by alternative therapeutic strategies using pathological indicators to inform treatment.
PubMed: 37583851
DOI: 10.12998/wjcc.v11.i21.5122 -
Digestive Diseases and Sciences Dec 2020Acute pancreatitis (AP) is a sudden inflammation of the pancreas that may be life-threatening disease with high mortality rates, particularly in the presence of systemic...
BACKGROUND
Acute pancreatitis (AP) is a sudden inflammation of the pancreas that may be life-threatening disease with high mortality rates, particularly in the presence of systemic inflammatory response and multiple organ failure. Oxidative stress has been shown to be involved in the pathophysiology of acute pancreatitis.
AIM
This study is designed to investigate the possible effect of mesna on an experimental model of cerulein-induced acute pancreatitis.
METHODS
Animals were divided into five groups: Group 1 served as a control group given the saline; group II (mesna group) received mesna at a dose of (100 mg/kg per dose, i.p.) four times; group III (acute pancreatitis group) received cerulein at a dose of (20 µg/kg/dose, s.c.) four times with 1-h intervals; group VI, cerulein + mesna, was treated with mesna at a dose of (100 mg/kg, i.p.) 15 min before each cerulein injection.
RESULTS
Animals with acute pancreatitis showed elevated serum amylase and lipase levels. Biochemical parameters showed increased pancreatic tumor necrosis factors-α (TNF-α) and interleukin-1β (IL-1β) levels. A disturbance in oxidative stress markers was evident by elevated pancreatic lipid peroxides (TBARS) and decline in pancreatic antioxidants' concentrations including reduced glutathione (GSH); superoxide dismutase (SOD); and glutathione peroxidase (GSH-Px). Histological examination confirmed pancreatic injury. Pre-treatment with mesna was able to abolish the changes in pancreatic enzymes, oxidative stress markers (TBARS, SOD, GSH and GSH-Px), pancreatic inflammatory markers (TNF-α, IL-1β) as well as histological changes.
CONCLUSIONS
Mesna mitigates AP by alleviating pancreatic oxidative stress damage and inhibiting inflammation.
Topics: Animals; Antioxidants; Ceruletide; Cholagogues and Choleretics; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Interleukin-1beta; Mesna; Oxidative Stress; Pancreas; Pancreatitis; Protective Agents; Rats; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 32088797
DOI: 10.1007/s10620-020-06072-1 -
American Journal of Otolaryngology 2020Mesna is a thiol compound effective in the connective tissue, which is used for its chemical dissector, mucolytic, mucosal damage preventive and antioxidant effects. The...
OBJECTIVE
Mesna is a thiol compound effective in the connective tissue, which is used for its chemical dissector, mucolytic, mucosal damage preventive and antioxidant effects. The aim of this study was to investigate Mesna's effects in easy dissection in type 4 tympanosclerosis cases and in the prevention of formation of new sclerotic plaques.
METHODS
11 patients were included in the study. All patients were in the Wielinga Kerr type 4 class of tympanosclerosis. All patients were administered a 100% concentration of Mesna in the middle ear during tympanosclerosis surgery. All patients underwent audiological evaluation before and 20 months after the operation. Air-conduction thresholds, bone-conduction thresholds and air-bone difference were statistically compared.
RESULTS
The patients were followed-up for a mean 20.48 ± 2.37 months. The mean preoperative air-conduction threshold of the patients was 58.09 ± 9.73 dB and the mean postoperative air-conduction threshold was 34.63 ± 15.46 dB and there was a significant difference. The mean preoperative bone-conduction threshold of the patients was 16.27 ± 5.47 dB and the mean postoperative bone-conduction threshold was 14.72 ± 6.11 dB and there was a significant difference. The mean preoperative air-bone gap of the patients was 41.81 ± 10.51, and the mean postoperative air-bone gap was 19.90 ± 12.48, and the difference was statistically significant.
CONCLUSION
Mesna prevented hearing loss related to type 4 tympanosclerosis and prevented the formation of new sclerotic structures in our follow-up period. We believe that this effect is due to the chemical dissector and antioxidant effects of Mesna.
Topics: Adolescent; Adult; Bone Conduction; Female; Follow-Up Studies; Hearing Loss; Humans; Male; Mesna; Middle Aged; Myringosclerosis; Perioperative Period; Time Factors; Treatment Outcome; Young Adult
PubMed: 32451291
DOI: 10.1016/j.amjoto.2020.102506 -
Iranian Journal of Pathology 2021The incidence of pericardial epithelioid angiosarcoma is rare. Angiosarcoma of pericardium may coat the pericardium in a diffuse fashion. Diagnosis of an angiosarcoma is...
The incidence of pericardial epithelioid angiosarcoma is rare. Angiosarcoma of pericardium may coat the pericardium in a diffuse fashion. Diagnosis of an angiosarcoma is challenging and may be easily mistaken as constrictive pericarditis. Herein, a case of primary pericardial angiosarcoma is reported in a 16-year-old female. Patient presented with chest pain and dyspnea on exertion, regarded as constrictive pericarditis. Pericardectomy was performed and histopathologic examination showed pleomorphic epithelioid cells exhibiting hyperchromatic nuclei, prominent nucleoli and eosinophilic cytoplasm arranged in sheets and occasionally lined irregular vascular spaces. Moreover, immunohistochemical staining revealed that tumor cells were positive for CD31 and vimentin. The patient received chemotherapy with adriamycin, ifosfamide, and mesna. Unfortunately, the patient died of cardiac involvement and pleural metastases less than three months following the operation. Primary pericardial angiosarcoma is rare and difficult to diagnose, especially epithelioid variant. Immunohistochemical assessment is required to confirm the final diagnosis.
PubMed: 34567196
DOI: 10.30699/IJP.2021.136440.2494 -
Cancer Reports (Hoboken, N.J.) Oct 2022Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS.
BACKGROUND
Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS.
CASE
A-44-years old woman with a chief complaint of pain in the epigastric area, itching, coughing, nausea, and vomiting was referred to the emergency department. Her medical history was LMS. She had taken Ifosfamide and mesna in her last chemotherapy. Seventy percent of her liver and her left kidney were removed 4 years ago to prevent the progress of the disease. Because of the increase in the level of creatinine and urea in the initial laboratory report, a Shaldon catheter was inserted for the patient, and she was under emergency dialysis for 3 h. In addition, during the six-day hospitalization period, dialysis was done two times. Finally, the patient was discharged with improved clinical tests accompanied by a twice-weekly dialysis order.
CONCLUSION
Ifosfamide is metabolized into chloroacetaldehyde, which can cause acute kidney injury. Recovery from acute kidney injury may not always be perfect and can lead to some degree of chronic kidney disease. Opposite to hemorrhagic cystitis, mesna is not effective in preventing ifosfamide's nephrotoxicity and N-acetylcysteine may be effective in the prevention of this nephrotoxicity.
Topics: Acetylcysteine; Acute Kidney Injury; Creatinine; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Urea
PubMed: 35830327
DOI: 10.1002/cnr2.1666 -
Journal of Oncology Pharmacy Practice :... Mar 2021Cyclophosphamide is an alkylating agent associated with significant toxicities, most importantly hemorrhagic cystitis. Many approaches including mesna use were...
BACKGROUND
Cyclophosphamide is an alkylating agent associated with significant toxicities, most importantly hemorrhagic cystitis. Many approaches including mesna use were established to reduce this toxicity. However, data on mesna efficacy are conflicting.
OBJECTIVE
To investigate the incidence of hemorrhagic cystitis in patients receiving cyclophosphamide therapy with or without mesna.
METHODS
A retrospective chart review was done on all adult patients receiving cyclophosphamide therapy with or without mesna at the King Saud University Medical City. The incidence of hemorrhagic cystitis was recorded. Patients receiving mesna were compared with those not receiving mesna. Data were reported as numbers and percentages, and appropriate statistical tests of association were used. This step was followed by a comprehensive literature review using appropriate keywords in PubMed from the inception of the database until August 2019. All studies of interest were reported.
RESULTS
A total of 718 patients' medical records were reviewed. The majority of the patients received mesna (n = 433, 60%). The mesna group had a greater incidence of hemorrhagic cystitis (3.5% vs. 0.4%, < 0.004) and received a significantly larger cumulative dose (3103 ± 1696 vs. 2465 ± 1528, < 0.001) mg of cyclophosphamide therapy. Our literature review revealed large differences in the conclusions of published trials with highly diverse study designs and populations, emphasizing on the need of large prospective trials to address this topic. Our study results do not support the use of mesna in preventing hemorrhagic cystitis. We found that the only influential factor in the development of hemorrhagic cystitis was the dose of cyclophosphamide therapy.
Topics: Adult; Antineoplastic Agents, Alkylating; Cohort Studies; Cyclophosphamide; Cystitis; Female; Hemorrhage; Humans; Male; Mesna; Middle Aged; Prospective Studies; Protective Agents; Retrospective Studies
PubMed: 32356687
DOI: 10.1177/1078155220920690